Biochemical Endocrine and Skeletal Findings in Adults with Fabry Disease: A Descriptive Single-Center Study

Background: Endocrine and skeletal findings have previously been reported in Fabry disease (FD), but their interpretation alongside Fabry-specific biochemical markers and multiorgan disease burden remains uncertain. This study descriptively characterized biochemical endocrine findings, vitamin D status, and age-appropriate DXA measurements in adults with FD receiving enzyme replacement therapy (ERT). Methods: This retrospective, single-center study screened 29 patients evaluated between January 2020 and December 2025, of whom 21 adults with genetically and/or enzymatically confirmed FD were included. Biochemical thyroid findings and HbA1c-defined dysglycemia were summarized separately as descriptive measures; no prespecified primary endpoint, composite endocrine outcome, or confirmatory outcome hierarchy was defined. A post hoc exploratory comparison was performed between patients with HbA1c-defined dysglycemia (HbA1c ≥ 5.7%; n = 7) and those without HbA1c-defined dysglycemia (HbA1c < 5.7%; n = 14). Vitamin D status and DXA findings were evaluated using age-, sex-, and menopausal-status-appropriate criteria. Exploratory analyses incorporated effect sizes, bootstrap confidence intervals, permutation tests, and Benjamini–Hochberg correction. Results: The mean age was 40.7 ± 14.5 years, and nine patients (42.9%) were male. The cohort was genetically concentrated, with c.851T>C (p.M284T) identified in 12/21 patients (57.1%). An elevated-TSH/non-elevated-FT4 biochemical pattern was observed in 2/21 patients (9.5%), and HbA1c-defined dysglycemia in 7/21 (33.3%). Vitamin D concentrations were <20 ng/mL in 16/21 patients (76.2%). DXA data were available for 20 patients. Among four postmenopausal women and four men aged ≥50 years, 5/8 (62.5%) had a minimum T-score within the osteoporosis range. Among seven premenopausal women and five men aged <50 years, 7/12 (58.3%) had a minimum Z-score ≤ −2.0, indicating BMD below the expected range for age. None of the 14 post hoc subgroup comparisons or 48 exploratory correlations remained significant after Benjamini–Hochberg correction. Conclusions: Thyroid, glycemic, vitamin D, and age-appropriate DXA measurements were descriptively characterized in this small, ERT-treated FD cohort. In the absence of an age-, sex-, and clinically matched comparator, the observed distributions cannot be interpreted as abnormalities attributable specifically to FD or as occurring more frequently than in an appropriate reference population. Moreover, no subgroup comparison or correlation remained significant after multiplicity correction. The data therefore do not demonstrate independent endocrine or skeletal relationships with Fabry disease burden and should be considered cohort-specific, descriptive, and hypothesis-generating.